Scarlets head coach Simon Easterby has selected a strong side for the clash with all of the Scarlets internationals involved in the match-day squad.
With some tough selection calls having to be made, there are three changes to the starting line-up that saw the Scarlets romp to a seven-try victory over Leinster at the last outing at Parc y Scarlets.
Jonathan Davies joins Scott Williams in midfield, Rhys Priestland starts at fly half while Phil John starts at prop with Rhodri Jones sidelined with a shoulder injury which was operated on last week.
Easterby said: "There's no doubt this is going to be a big night, and one to capture the imagination of supporters, coaches and players alike as these derbies have done for many years - and it's great that we'll have a packed house here on Friday evening and an atmosphere fitting of a big West Wales derby.
"Welsh regional rugby comes alive at these fixtures and there's no need for any introduction with all the history, heritage and passion of between our respective rugby communities.
"The Ospreys may not have had the start they wanted, but a few months ago they were the league champions and know they have the quality within their ranks to turn things around.
"Last season we held them to a draw at the Liberty as well as decent win here at Parc y Scarlets but before that we lost a run of games against them, so we're not getting ahead of ourselves and form or favourite tags don't mean much in these fixtures."
Easterby said that it was encouraging to see his Scarlets team take their chances well in their opening three rounds with a try count of 14 from three games.
"What we have done well is take our opportunities - we created plenty last season, but weren't executing as well as we have in these opening games. The players have shown the mentality and clinical edge that makes the difference."
Ospreys Head Coach, Steve Tandy, said: "This derby is always a big game, something special, and no doubt that will be the case on Friday. It's great that local rivalries still mean so much, that despite the changes in the game we can still have these big derby matches.
"I don't think there's any doubt that who will be going into the game as favourites given recent results. They have been playing good rugby, scoring tries, and their tails will be up, but we'll be doing everything we can to ensure that our fans there on Friday night can head back this side of the bridge proud of their team.
"I've already spoken about how disappointed we were with the performance on Friday night. The overall performance wasn't acceptable and the players are well aware of that. We have our own internal standards that we expect from any Ospreys team and on Friday night in particular we didn't reach those standards."
There will be a minute's silence observed at kick-off in memory of the loss of Ulster's Nevin Spence and his father and brother who died tragically last weekend in a farming accident.